2wkl

VELAGLUCERASE ALFA
(see also Treatment of Gaucher disease)

 The structural alignment of the crystal structure of velaglucerase alfa (colored red) reveals that it is very similar to those of the recombinant GlcCerase produced in Chinese hamster ovary cells (imiglucerase, Cerezyme®, colored blueviolet, 2j25) and in transgenic carrot cells (prGCD, 2v3f). Superposition of the two individual molecules in the asymmetric unit of velaglucerase alfa and imiglucerase demonstrates striking similarity between positions of catalytic residues E235 and E340 (colored orange) in all 4 molecules. The position of H311 is also very similar in all 4 molecules, whereas the conformations of 3 other active site residues W312, Y313, and, especially N396 are somewhat different. The active site residues (except E235 and E340 ) of the two individual molecules in the asymmetric unit of velaglucerase alfa are colored: subunit A (red), subunit B (lime) and of imiglucerase: subunit A (blueviolet) , subunit B (magenta). Imiglucerase and pr-GlcCerase contain a histidine at residue 495 (blueviolet), whereas velaglucerase alfa contains arginine (red). Mutations which cause Gaucher disease, R496 and D474 are close to R495 near the N-terminus of GlcCerase. The <scene name='2wkl/Al/11'>velaglucerase alfa (<font color='blue'>its glycans are colored blue ) and <scene name='2wkl/Al/12'>imiglucerase (<font color='magenta'>its glycans are colored magenta ) have different carbohydrate composition. This difference in glycosylation causes the increased cellular uptake of velaglucerase alfa over imiglucerase and could lead to improvement of treatment of Gaucher disease.

About this Structure
2WKL is a 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference
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